Trimodal Therapy Consideration

[JohnK59]

My TURBST followup was December 7th with a 5 cm, high grade, muscle invasive tumour lower, left posterior side of bladder.

The pathology report was sent to me on December 15th and reads all the above plus Lymphvascular Invation  :Present.  

I’m 64 yrs of age have no other health ailments.

I have a month to wait for a TMT screening TURBST  at UHN.

I think TMT acceptance may be a long shot.

I think I need to opt for the RC and hope for an early start to chemo.

Anyone familiar with the seriousness of Lymphvascular Invation  :Present. 

 

 

 

[Nightingale]

Hi JohnK59,

I am sorry to hear about your situation.   I hope someone with experience replies soon.  In the meanwhile please hang in there.  I wanted to let you know that we can also try and find you a peer support volunteer with whom you can have a discussion with – ask questions and so on.  Let me know if this is of interest to you.

My Best,

 

[Joe]

Hi John,

I am somewhat familiar with TMT, so I would try to answer your question.  I also recall someone in this discussion form had TMT at UHN, so I hope the patient can add from his expereince.

UHN (UT) in Canada and Massachusetts General Hospital (MGH) in the US have been known for TMT in North America.   Recent joint publication (May 2023) of retrospective study  by  UHN, MGH and University of Southern California stated that there were no difference in term of 5 year survival rate between RC and TMT when TMT patients were carefully selected.  Carefully selected patients are the key.  In the study, all patients had solitary tumours less than 7 cm, no or unilateral hydronephrosis, and no extensive or multifocal carcinoma in situ, also all patients were T2-T4N0M0 muscle-invasive urothelial carcinoma of the bladder.    your tumor was a solitary, 5 cm and with no CIS.  I do not know how they determine if  your kidney and upper tract condition to exclude if you do have hydronephrosis.  Lets assume there are no hydronephrosis.  Then like you will meet the criteria to be a candidate for TMT except the confirmation lymph node negative (N0  – N zero).    I think it requires something like CT scan to confirm if N0.  Then, I assume that  your question is how LVI:Present  relates to N0 or N+.   According to the study done in 2004, LVI:Present , pT stage, and grade sustained statistical significance as independent factors for N+.  It does not mean LVI:Negative always N0.

Between June 1997 and December 1999, 418 patients had RC and bilateral pelvic lymphadenectomy.

Of 418 patients,  110 patients were N+.   Of 110 patients with N+,   69 patients were LVI:Present and 41 patients were LVI:Negative   Of 418,  133 were LVI:Present and 285 were LVI Negative.

The study used multivariable analysis of N+ relative to Stages, Grade and LVI status.  Note that I do not know exactly how they analyzed the data statistically, but I think we can understand intuitively the result.

LVI:Negative        Regression Estimate (RE) 0.00     SE  __    RR 1.00     p Value     p Value is like confidence level

LVI:Present          RE 1.38   SE 0.29    RR 3.99   p Value  0.001       If p Value < 0.05, it is considered statistical significant.

I think RR means Rate Ration.  So, if  LVI:Negative  RR = 1.00 meaning if we assume LVI:Negative will have N+ at ration of 1, then LVI:Present will have N+ at ratio of 3.9 or 3.9 times more than LVI:Negative?  Anyway, the study indicates the likeliness of having N+ is higher with LVI:Present vs LVI:Negative.   But, when we look at how pT Stages affect likeliness of having N+ is much higher, RR 3.9 does not seem that significant.  See below the relation between pT Stages to N+.

Stage

PIS/PI  (Ta, CIS, T1)         RE   0          RR  1.00

pT2a    RE  1.05      RR 2.84    p  value  0.024    – statistical insignificant

pT2b    RE  2.57      RR 13.05   p value < 0.001

pT3      RE  2.99      RR 19.70   p value <0.001

pT4      RE  3.59      RR  36.35  p value < 36.65

What this tells is that the likeliness (RR=3.99) of LVI:present  having N+ is about the same as the likeliness (RR=2.84) of pT2a having N+, and much lower than the likeliness  (RR=13.05) of pT2b having N+ or pT3 (RR=19.70) and pT4 (RR= 36.35).  In other words,  I interpret this as  in terms of possibility of N+,  pT stages have much stronger relation with possibility of N+ than LVI:Present.   Accordingly, I do not think LVI:Present will be used to restrict you from TMT.  Otherwise, it would say so in the recent study by UHN, MGH and USC or other presentations I have watched on TMT.    Nevertheless,  you may want to have the copy of the 2004 study for TMT screening.

The title of the study is “Nodal Involvement in Bladder Cancer cases treated with radical cystectomy: Incidences and Prognosis”.     For some reasons, often I lose the entire writing when I specify the link, so you can google to find the article.  The study was done by the department of urology-nephrology center in Egypt.  I usually trying to find similar studies by better known cancer centers but  I have that this study had relevant information that you wanted.  Also the study was published by American Urological Association, so they must have gone through peer reviews.

• This reply was modified 1 year, 4 months ago by theresab.

[JohnK59]

Hello Joe,

Thank you for your responce.

Alot of very technical information that I am still wading through.  My doctor is working concurrently toward both procedures.  I have seen an oncologist who has me booked for chemo information session January 2nd and an immune system booster shortly there after.  This could be closely followed by my 1st cycle of chemo although I may need to hold off on that because my Toronto General screening for TMT in on January 17th.

I dont want to be disqualified for TMT by starting chemo prior to UHN’S screening.

I’m sure I’ll get my answer shortly after my screening at UHN.  Waiting an extra 3 weeks before chemo worries me.

 

[Joe]

Hi John,

A Happy Holiday Season !!

I had assumed that the your question was if Lymphvascular Invasion  :Present would negatively affect you to qualify TMP at UHN/UT.   I was trying to explain that it should not affect, and  the study substantiates the claim.

The patients selection criteria form TMT  has evolved and now it seems that UHN/UT wants to choose patients who would likely to have similar prognosis, i.e. progression free survival rate and over all survival rate, compared to radical cystectomy.   Dr. Girish S. Kulkarni of UHN/UT lists the criteria for ideal patients for TMT as follows.    The description of your pathology after TURBT seems to indicate that you meet most of the requirement.

• T2 is preferred   –   Bladder wall consists of Epithelial tissue, connective tissue, muscle tissue, fat.  T2 means that tumour has progressed to muscle tissue but not fat layer (T3).
• Tumours < 5 cm ( <7 cm)
• Single tumour
• No hydronephrosis
• Minimal to no Carcinoma In-Situ (CIS) involvement.
• Good bladder function and capacity
• Patients who can follow up treatment and diagnosis schedule for TMT

The above selection criteria were further validated by the joint study by UT, MGH (US) and USC (US) that TMT patients who meet similar requirement indeed result in similar prognosis compared with RC in terms of progression free survival rate.  The result of the joint study was presented by Dr. Zlotta of UT in 2023 American Society of Clinical Oncology (ASCO) conference.    What I have noticed is that the study selected only patients with with clinical stage T2–T4N0M0 MIBC, meaning that no lymph node positive patients were selected.   I think imaging such as CT scan is necessary to clinically find out lymph node positive (N1,2,3).  So, it is possible UHN/UT may arrange CT scan as part of patient’s selection process for TMT.  It is something which can be clarified by your contacting UHN/UT or during the meeting on January 17.    The study I mentioned previously showed patients with lymphvascular invasion :present had higher chance of having lymph node positive pathologically compared those with no lymphvascular invasion :present.   Note patients with no lymphvascular invasion :present also had lymph node positive pathologically.   Pathological positive means that cancer cells were found when pathologist analyzed  dissected lymph node by microscope.   Because it is possible that pathological lymph node can be positive either lymphvascular invasion :present or not present though higher probability with lymphvascular : present, I do not think lymphvascular invasion is used as one of selection criteria for TMT candidates. You can also clarify this with UHN/UT if you like.

As matter of fact, UHN/UT treatment protocol seems to assume that patients for TMT may have cancer cells in lymph nodes already which are not detectable by imaging such as CT scan.  To deal with it,  UHN/UT treatment protocol is to prescribe neoadjuvant chemotherapy first.   Then later on radiation targets not only bladder but also pelvic, indicating that the radiation also targets lymph nodes.

Below is the link to the more recent presentation by Dr. Girish S. Kulkarni of UHN/UT on how UHN/UT selects ideal candidates for TMT and explaining the treatment protocol of UHN/UT to urologists of University of British Columbia.

[JohnK59]

Good day Joe,

Thank you for this very useful information.  I wrote to you or at least I thought I did this morning.  Seems I messed up because I don’t see it.

Very useful information.  Learned a few things for certain.  Havent finnished the video yet but I will.

One year rehab and drastic weight loss after RC were not mentioned by my doctor.

I have to hold off on chemo and hear what Dr Zlotta has to say on the 17th.

Thank you kindly Joe.

John

 

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